n-n--4-xylylenebis(pyridinium) and 1-2-bis(10(2--4--hexadienoyloxy)decanoyl)-sn-glycero-3-phosphocholine

The potential biomedical utility of the photoinduced destabilization of liposomes depends in part on the use of green to near infrared light with its inherent therapeutic advantages. The polymerization of bilayers can be sensitized to green light by associating selected amphiphilic cyanine dyes, i.e. the cationic 1,1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine (DiI), or the corresponding anionic disulfonated DiI (DiI-DS), with the lipid bilayer. The DiI sensitization of the polymerization of 1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine/1,2-bis[10-(2', 4'-hexadienoyloxy)-decanoyl]-sn-glycero-3-phosphocholine liposomes caused liposome destabilization with release of encapsulated aqueous markers. In separate experiments, similar photosensitive liposomes were endocytosed by cultured HeLa cells. Exposure of the cells and liposomes to 550 nm light caused a net movement of the liposome-encapsulated 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) from low pH compartment(s) to higher pH compartment(s). This suggests that photolysis of DiI-labelled liposomes results in delivery of the contents of the endocytosed liposomes to the cytoplasm. The release of HPTS into the cytoplasm appears to require the photoactivated fusion of the labelled liposomes with the endosomal membrane. These studies aid in the design of visible light sensitive liposomes for the delivery of liposome-encapsulated reagents to the cytoplasm.

Topics: Arylsulfonates; Carbocyanines; Color; Cytoplasm; Drug Carriers; Endocytosis; Endosomes; Fluorescent Dyes; HeLa Cells; Humans; Hydrogen-Ion Concentration; Light; Liposomes; Membrane Fusion; Naphthalenes; Phosphatidylcholines; Phosphatidylethanolamines; Photolysis; Pyridinium Compounds; Sulfonic Acids; Temperature; Ultraviolet Rays